Aptamer联合ECM智能材料靶向递送miR-26a原位诱导骨再生研究

Efficient recruitment of endogenous stem cells to homing and targeted regulation of osteogenesis/angiogenesis is a key issue in the region of bone biomaterials inducing bone regeneration in situ. However, traditional bone biomaterials have inferior capability of cell recruitment and induction due to insufficient recognition to endogenous stem cells. Recent studies have shown that the aptamer could specifically recognize and target cells, and has the advantages of easy synthesis, low immunogenicity and high safety. This project aims to construct a novel osteoinductive material sensitive to endogenous stem cells. That would use a pre-established Composite Scaffold Containing Small Intestinal Submucosa and Mesoporous Bioactive Glass (SIS/MBG) which possess certain osteogenic angiogenic ability, and load SIS/MBG with aptamer-functionalized nanoparticle delivery system by nucleic acid technology. The natural extracellular matrix (ECM) derived composite, which is rich in molecular signals for cell homing, combined with aptamer efficiently recruit endogenous stem cells homing. It could control the release of osteogenic/angiogenic factor miR-26a while it recognizes BMSC, and efficiently targeted delivery miR-26a to BMSC through aptamer. The novel osteoinductive material can overcome the shortcoming of traditional bone biomaterials, such as inferior capability of the recognition and induction of endogenous stem cells. It would significantly improve the regulation efficiency of endogenous stem cells, and provide a new strategy and scientific basis to construct intelligent biological materials to induce bone regeneration in situ.

高效募集内源性干细胞归巢、靶向调控其成骨/成血管分化是当前骨修复材料实现原位骨再生亟待解决的关键问题。传统骨修复材料因缺乏对内源性干细胞特异识别导致细胞归巢、诱导能力不足。最新研究表明核酸适配体Aptamer可以特异识别结合靶细胞，具有合成容易、无免疫原性和安全性高等优势。本项目拟基于前期已构建具有一定成骨成血管活性的小肠粘膜下层脱细胞基质ECM/介孔生物玻璃多孔支架，通过核酸技术负载Aptamer功能化的纳米颗粒递送体系，构建内源性干细胞响应的新型骨诱导材料。富含归巢分子信号的ECM支架联合Aptamer能高效特异性募集内源性BMSC归巢，并通过Aptamer感应微环境BMSC存在来介导成骨成血管调控因子miR-26a靶向递送，实现原位诱导骨再生。该骨诱导材料克服目前生物材料对内源性干细胞识别、响应不足，显著提高对干细胞的调控效率，为构建智能生物材料原位诱导骨再生提供新的思路和科学依据。

高效募集内源性干细胞归巢、靶向调控其成骨/成血管分化是当前骨修复材料实现原位骨再生亟待解决的关键问题。传统骨修复材料因缺乏对内源性干细胞特异识别导致细胞归巢、诱导能力不足。最新研究表明核酸适配体Aptamer可以特异识别结合靶细胞，具有合成容易、无免疫原性和安全性高等优势。本项目拟基于前期已构建具有一定成骨成血管活性的小肠粘膜下层脱细胞基质ECM/介孔生物玻璃多孔支架，通过核酸技术负载Aptamer功能化的纳米颗粒递送体系，构建内源性干细胞响应的新型骨诱导材料。富含归巢分子信号的ECM支架联合Aptamer能高效特异性募集内源性BMSC归巢，并通过核仁素响应释放、Aptamer感应微环境BMSC存在来介导成骨成血管调控因子miR-26a靶向递送，实现原位诱导骨再生。该骨诱导材料克服目前生物材料对内源性干细胞识别、响应不足，显著提高对干细胞的调控效率，为构建智能生物材料原位诱导骨再生提供新的思路和科学依据。